Chlorinated aromatic pollutants such as the polychlorinated biphenyls, benzenes, terphenyls, and naphthalenes are among the most persistant and widespread chemicals in the environment and these have been identified in wildlife and human tissue. This research proposal is concerned with a detailed investigation of the uptake, metabolism, mechanism of metabolism, tissue and organ levels of the pollutants and their metabolites in model mammalian systems (rabbit, rat). The effects of both degree of chlorination and substitution on the in vivo pollutant pharmacodynamics will also be evaluated. The in vitro metabolism (i.e., detoxication) of the chlorinated aromatic pollutants using liver microsomal enzymes will also be investigated. The binding of the "metabolically activated" arene oxides with cellular macromolecules (i.e., toxication) such as RNA, DNA, protein, lipid and polysaccharide will be studied with particular emphasis on the precise identity of the bound macromolecule, the specificity of the binding and the effects of chemical inducers on the detoxication/toxication ratios. Parallel to these studies the pollutant substrates and their diverse metabolites will be screened in the Ames bacterial test for mutagenic and carcinogenic activity using specific mutant strains of Salmonella typhimurium.